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Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles

  1. Willem J. M. Mulder1,2,3,
  2. Gustav J. Strijkers1,
  3. Karen C. Briley-Saboe2,3,
  4. Juan C. Frias2,3,
  5. Juan Gilberto S. Aguinaldo2,3,
  6. Esad Vucic2,3,
  7. Vardan Amirbekian2,3,
  8. Cheuk Tang2,3,
  9. Patrick T. K. Chin4,
  10. Klaas Nicolay1,
  11. Zahi A. Fayad2,3,*

Article first published online: 28 NOV 2007

DOI: 10.1002/mrm.21315

Issue

Magnetic Resonance in Medicine

Magnetic Resonance in Medicine

Volume 58, Issue 6, pages 1164–1170, December 2007

Additional Information

How to Cite

Mulder, W. J. M., Strijkers, G. J., Briley-Saboe, K. C., Frias, J. C., Aguinaldo, J. G. S., Vucic, E., Amirbekian, V., Tang, C., Chin, P. T. K., Nicolay, K. and Fayad, Z. A. (2007), Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles. Magn Reson Med, 58: 1164–1170. doi: 10.1002/mrm.21315

Author Information

  1. 1

    Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands

  2. 2

    Institute for Translational and Molecular Imaging, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA

  3. 3

    Eva and Morris Feld Estate Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA

  4. 4

    Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, Eindhoven, The Netherlands

*Imaging Science Laboratories, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029

Publication History

  1. Issue published online: 28 NOV 2007
  2. Article first published online: 28 NOV 2007
  3. Manuscript Accepted: 4 MAY 2007
  4. Manuscript Revised: 2 APR 2007
  5. Manuscript Received: 14 DEC 2006

Funded by

  • The Sixth Framework Programme of the European Community for Research Technical Development
  • Demonstration Activities project Diagnostic Molecular Imaging (EC-FP6 project DiMI). Grant Number: LSHB-CT-2005-512146
  • Besluit Subsidies Investeringen Kennisinfrastruct (BSIK). Grant Number: BSIK03033
  • National Institutes of Health National Heart, Lung, and Blood Institute (NIH)/NHLBI. Grant Numbers: R01 HL71021, R01 HL78667

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Keywords:

  • molecular imaging;
  • macrophage activity;
  • pegylated micelles;
  • quantum dots;
  • MRI

Abstract

Pegylated, fluorescent, and paramagnetic micelles were developed. The micelles were conjugated with macrophage scavenger receptor (MSR)-specific antibodies. The abdominal aortas of atherosclerotic apoE-KO mice were imaged with T1-weighted high-resolution MRI before and 24 h after intravenous administration of the contrast agent (CA). Pronounced signal enhancement (SE) (up to 200%) was observed for apolipoprotein E knockout (apoE-KO) mice that were injected with MSR-targeted micelles, while the aortic vessel wall of mice injected with nontargeted micelles showed little SE. To allow fluorescence microscopy and optical imaging of the excised aorta, the micelles were made fluorescent by incorporating either a quantum dot (QD) in the micelle corona or rhodamine lipids in the micelle. Ultraviolet (UV) illumination of the aorta allowed the identification of regions with high macrophage content, while MSR-targeted rhodamine micelles could be detected with fluorescence microscopy and were found to be associated with macrophages. In conclusion, this study demonstrates that macrophages in apoE-KO mice can be effectively and specifically detected by molecular MRI and optical methods upon administration of a pegylated micellar CA. Magn Reson Med 58:1164–1170, 2007. © 2007 Wiley-Liss, Inc.

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